An estimated one third of the world's population is infected with Mycobacterium tuberculosis, and it is the leading cause of death among adults by an infectious disease worldwide. TB control using DOTS (Directly Observed Short Therapy, short course) to successfully diagnose, treat and follow sputum-smear positive TB cases is a priority of the World Health Organization (WHO), but there is growing recognition that DOTS alone will not be enough to control or eradicate TB given the extended duration of treatment and the emergence of drug-resistant forms of M. tuberculosis. New methods are needed to quantify the impact of ongoing TB transmission and the importance of preventive strategies. The focus of this research will be an evaluation of community- based TB transmission dynamics at a field site in Southern Mexico. Molecular epidemiology provides important insights into the transmission dynamics of tuberculosis, but because it relies upon mycobacterial cultures, it can only track active cases. The proposed research will integrate conventional tuberculin skin test survey methodology into an ongoing population-based research project so that we may track infection as well as disease and test hypotheses about alternative strategies for controlling TB infection. The specific aims are: 1) to describe the epidemiology of TB infection caused by culture-confirmed cases of M. tuberculosis; 2) to identify risk factors for TB infection, stratified by the biologic characteristics of the strains of M. tuberculosis and the gender, age group, and social setting of the index cases; 3) to determine the specificity and predictive value of contact tracing by comparing the RFLP patterns of cases and those arising among their contacts; and 4) to develop cost- effectiveness models of appropriate screening strategies and interventions to control TB infection. The research will also generate important baseline data for the future testing of new diagnostics and vaccines. This project will provide an ideal vehicle for additional, mentored training and research to develop the PI's long standing career interest in international infectious disease research. The grant award will build on previous work and provide training in areas new to the candidate, such as biomedical techniques and cost-effectiveness modeling. Her technical training in epidemiology and biostatistics, prior epidemiologic research studies, and extensive familiarity with Latin America fit perfectly with the strengths and needs of a well established field site in Veracruz, Southern Mexico.